Light irradiation therapy is used for the treatment of various blood diseases to, e.g., eliminate immunogenicity in cells, inactivate or kill selected cells, inactivate viruses or bacteria, or activate desirable immune responses. For example, it is known to use the photoactivatable drug psoralen to treat pathogenic blood cells, such as lymphocytes, in an extracorporeal photopherisis (ECP) procedure in which the patient receives 8-methoxypsoralen (8-MOP), blood is withdrawn from the patient, the white cells separated (typically by centrifugation), and subjected to UV light to activate the 8-MOP molecules. The photoactivated 8-MOP alters the DNA of the pathogenic leukocytes, and the fluid with the altered leukocytes is reinfused back into the patient to induce an immune system response.
A difficulty in performing phototherapy is the delivery of the proper dose of light energy to the photoactivatable material in the suspension, particularly if the suspension includes material that is not substantially transparent to light so that it attenuates the light energy intended for photoactivation, or if the target cells are not uniformly distributed on the fluid surface, in which case target cells closest to the surface may serve to attenuate light energy with respect to those target cells beneath the surface.
A method for delivering a desired dose of light energy to a suspension is disclosed in U.S. Pat. No. 6,219,584, to Therakos, Inc. This patent is directed to an “online” photopheresis system that includes both the blood separation device and the photoactivation device in an integrated, closed system. In this and other Therakos systems, a complex algorithm is used to determine the emitted dose (“fluid light energy value” or FLEV) needed to achieve the target dose (the “target's effective light energy value” or TELEV) that is to be delivered to the targeted leukocytes (mononuclear cells or MNC). This algorithm requires knowledge of the thickness ratio of the product, as well as the light transmittance value of the product that is measured for every product using a hematocrit sensor.
In “offline” methods, (such as those practiced when using the phototherapy systems available from Macopharma SA or Vilber Lourmet), the UV dose is monitored by sensors which are angled to detect UV light emitted from the UV bulbs as well as that reflected from the mirrored surface behind each set of bulbs (and presumably less light is reflected back if the treated cell product is absorbing more light). This method does not fully account for the UV light being absorbed by the red cells and plasma, and operators are required to manually measure the product hematocrit and adjust it (if necessary) to lower than 2% because the UV dose delivered at higher hematocrits is unknown (and likely insufficient).
In accordance with the method described below, a dedicated hematocrit sensor is not required, but only moderate control of a preset product volume and hematocrit of the suspension to be treated is required. The desired light dose to be received by the target cells is determined based on the therapeutic response of the target cells, thus providing for a more precise therapeutic result than simply applying a correction factor to the emitted light dose. The desired light dose to be received by the target cells is also more accurately controlled by UV light sensors that account for variation in UV light emission.